We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Continued research investigation of the N-alkyl substituent of this… (More)

A value of k(H) = 1.5 x 10(-)(3) M(-)(1) s(-)(1) has been determined for the generation of simple p-quinone methide by the acid-catalyzed cleavage of 4-hydroxybenzyl alcohol in water at 25 degrees C… (More)

The pH-rate profile of first-order rate constants for the lactonization of Indinavir in aqueous solutions with ionic strength I = 1 (KCl) at 40 degrees C is reported. The lactonization reaction is a… (More)

[structure: see text] We propose that controversy concerning the mechanism for solvolysis at tertiary carbon is semantic and can be avoided by making a clear distinction between (1) nucleophilic… (More)

The Hedgehog (Hh) signaling pathway regulates cell proliferation and differentiation in developing tissues, and abnormal activation of the Hh pathway has been linked to several tumor subsets. As a… (More)

Structure-based rational design led to the discovery of novel inhibitors of the MDM2-p53 protein-protein interaction. The affinity of these compounds for MDM2 was improved through conformational… (More)

Rate constant ratios for addition of the three nucleophilic sites of phenol to the 1-(4-methoxyphenyl)ethyl carbocation (1+) in 50/50 (v/v) trifluoroethanol/water were determined from the relative… (More)